The thyroid hormone receptor is a chromatin associated protein which appears to mediate the action of thyroid hormone in mammalian cells. In cultured GH1 cells, a rat pituitary cell line, the chromatin associated receptor appears to represent a steady state value which is dependent upon receptor synthesis and receptor turnover. In these cells, L-T3, L-T4, and other thyroid hormone analogues elicit a time and dose dependent reduction in nuclear receptor levels which appear to be directly related to their relative affinity for the receptor binding site. In addition, sodium n-butyrate and other aliphatic carboxylic acids elicit a reduction in thyroid hormone nuclear receptor levels without altering total cell protein synthetic rates. This reduction appears to be secondary to an effect of the aliphatic carboxylic acids on inhibiting chromatin associated deacetylases which is reflected as an increase in acetylation of histones H3 and H4 of the nucleosome core. Micrococcal nuclease and DNase 1 digestion studies indicate that the receptor is released as a 6.5 S form which is significantly larger than the form which can be extracted from nuclei by 0.4 M KC1 (3.8 S). Preliminary studies indicate that the 6.5 S is converted to a 3.8 S form by raising the salt concentration but goes through an intermediate 5.0 S form suggesting that there is another protein component(s) with which the receptor associates. Furthermore, unlike the 3.8 S form, the 6.5 S form does not appear to bind to DNA suggesting that the 6.5 S form also reflects receptor associated with the small DNA fragment. In this study we propose to study the biochemical characteristics of the 6.5 S receptor complex released by chromatin digestion to define whether it is associated with the DNA fragment which may reflect with the component with which the receptor normally associates with nuclei and to determine whether other regulatory proteins remain associated with this complex.